High glucose promotes retinal endothelial cell migration through activation of Src, PI3K/Akt1/eNOS, and ERKs.
Hyperglycemia impacts retinal vascular function and promotes the development and progression of diabetic retinopathy, which ultimately results in growth of new blood vessels and loss of vision. How high glucose affects retinal endothelial cell (EC) properties requires further investigation. Here we determined the impact of high glucose on mouse retinal EC function in vitro. High glucose significantly enhanced the migration of retinal EC without impacting their proliferation, apoptosis, adhesion, and capillary morphogenesis. The enhanced migration of retinal EC under high glucose was reversed in the presence of the antioxidant N-acetylcysteine, suggesting increased oxidative stress under high-glucose conditions. Retinal EC under high-glucose conditions also expressed increased levels of fibronectin, osteopontin, and alpha(v)beta(3)-integrin, and reduced levels of thrombospondin-1. These changes were concomitant with sustained activation of the downstream prosurvival and promigratory signaling pathways, including Src kinase, phosphatidylinositol 3-kinase/Akt1/endothelial nitric oxide synthase, and ERKs. The sustained activation of these signaling pathways was essential for enhanced migration of retinal EC under high-glucose conditions. Together, our results indicate the exposure of retinal EC to high glucose promotes a promigratory phenotype. Thus alterations in the proangiogenic properties of retinal EC during diabetes may contribute to the development and pathogenesis of diabetic retinopathy.
Huang
Qiong
Q
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI 53792-4673, USA.
Sheibani
Nader
N
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D016023:Integrins / Q000378:metabolism; D051379:Mice; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012171:Retinal Vessels / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D019061:src-Family Kinases / Q000378:metabolism
D016023:Integrins; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose